Autism is becoming increasingly common in the United States. The latest survey by the Centers for Disease Control and Prevention (CDC) shows that 2 percent of children in the U.S. have autism spectrum disorder (ASD), which is characterized by a range of symptoms from repetitive behaviors to communication difficulties and mental retardation.
Although genetics plays a major role in the development of the condition, it isn't the only factor leading to ASD. Researchers are already looking at what occurs during pregnancy and found another possible factor: high levels of chloride ions in the body during birth.
In a new study published in the journal Science Feb. 7, a group of researchers led by Yehezkel Ben-Ari of the Mediterranean Institute of Neurobiology (INMED) in Marseille, France, engineered pregnant mice to give birth to offspring with autistic behavior. They found that giving the mice bumetanide, a diuretic used for treating fluid retention and high blood pressure, to lower their chloride levels results in offspring with no symptoms of autism.
"We have proven the concept that in autism chloride is elevated and perhaps our diuretic acts by reducing that. The evidence was lacking until now," Ben-Ari said. "We showed that if you deliver diuretic to the mother before birth and delivery, then the offspring have so to speak been cured... whereas if you block oxytocin, you get autism."
Oxytocin, a hormone responsible for contraction of the uterus during childbirth works like a diuretic. It reduces chloride levels within the nerve cells so when this chemical is blocked, levels of chloride ions continue to remain high after birth which causes autism.
Here's how it works: during childbirth, oxytocin prompts a neurotransmitter called gamma aminobutyric acid, or GABA to shift from stimulating neurons in the fetus' brain to quieting them down. When this does not happen, the neurons remain in their excited state and chloride builds to higher-than-normal levels.
"During birth and delivery there is an extremely abrupt loss of chloride triggered by the release of oxytocin during labour," Ben-Ari explained. "If you block oxytocin during delivery you block this protective mechanism."
Although the study by the French researchers does not suggest a way of treating humans prenatally to prevent autism, its findings provide crucial information needed for further research on the condition. Andrew Zimmerman, a pediatrician at the Lurie Center for Autism at Massachusetts General Hospital in Boston, said there is research interest for biomarkers that could one day detect and prevent autism much earlier in life.
"I think that an early diagnosis of autism spectrum disorder, coupled with a [diuretic] drug such as bumetanide or other regulators acting to reduce aberrant brain activities that perturb neuronal activities, are likely future therapies," Ben-ari said. Ben-ari and his colleagues have already come up with a patented version of bumetanide and have formed the company Neurochlore in Marseilles, France, to test the drug on French and Spanish children with autism. The results of the test are expected by the end of this year.
